The purpose of this project is to identify the determinants of type 2 diabetes, obesity, and other chronic diseases in the Pima Indians, and elucidate their natural history. Genetic and environmental risk factors for type 2 diabetes have been studied. The residents of the study area, approximately 8000 people, have participated in a longitudinal population study since 1965, allowing observations of the natural history of diabetes mellitus. Risk factors for obesity, hypertension, and nephropathy are also studied, along with the relationships of these diseases to diabetes and their effects on mortality rates. The genetics of diabetes is studied by means of family studies and relationships of genetic markers to disease. The roles of obesity, serum insulin concentrations, impaired glucose regulation, occupational and leisure-time physical activity and diabetes in relatives are assessed. Studies of the genetics of type 2 diabetes and obesity are described in project report # Z01 DK 69028 PECR. Behavioral risk factors contribute to the incidence of type 2 diabetes in this population, as self-reported physical inactivity predicts diabetes. There was no relationship, however, with self-reported alcohol consumption. A variety of metabolic variables, such as hyperinsulinemia, hyperlipidemia, and obesity, also predict diabetes, but each of these entities appears to supply unique information about diabetes risk.